REVIEW ARTICLEpublished: 02 August 2013

doi: 10.3389/fnhum.2013.00423

The significance of the subplate for evolution anddevelopmental plasticity of the human brainMiloš Judaš*, Goran Sedmak and Ivica Kostovic

Section of Developmental Neuroscience, Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb,Croatia

Edited by:

Roberto Lent, Federal University ofRio de Janeiro, Brazil

Reviewed by:

Zoltan Molnar, University of Oxford,UKKarl Zilles, ForschungszentrumJülich, Germany

*Correspondence:

Miloš Judaš, Section ofDevelopmental Neuroscience,Department of Neuroscience,Croatian Institute for BrainResearch, University of ZagrebSchool of Medicine, Šalata 12,10000 Zagreb, Croatiae-mail: mjudas@hiim.hr

The human life-history is characterized by long development and introduction of newdevelopmental stages, such as childhood and adolescence. The developing brain hadimportant role in these life-history changes because it is expensive tissue which uses upto 80% of resting metabolic rate (RMR) in the newborn and continues to use almost 50%of it during the first 5 postnatal years. Our hominid ancestors managed to lift-up metabolicconstraints to increase in brain size by several interrelated ecological, behavioral andsocial adaptations, such as dietary change, invention of cooking, creation of family-bondedreproductive units, and life-history changes. This opened new vistas for the developingbrain, because it became possible to metabolically support transient patterns of brainorganization as well as developmental brain plasticity for much longer period and withmuch greater number of neurons and connectivity combinations in comparison to apes.This included the shaping of cortical connections through the interaction with infant’ssocial environment, which probably enhanced typically human evolution of language,cognition and self-awareness. In this review, we propose that the transient subplate zoneand its postnatal remnant (interstitial neurons of the gyral white matter) probably servedas the main playground for evolution of these developmental shifts, and describe variousfeatures that makes human subplate uniquely positioned to have such a role in comparisonwith other primates.

Keywords: cerebral cortex, neuron number, life-history, metabolic cost, subplate zone

INTRODUCTIONWe humans have large brains, and flatter ourselves to be smart.Accordingly, we are prone to think that “bigger is better” andto assume that larger (i.e., more encephalized) brains shouldhave larger computational and cognitive abilities (for a com-prehensive and historical review, see Herculano-Houzel, 2009,2011a,b, 2012a). Some recent versions of this notion assumethat improved cognition does not depend on relative brainsize (i.e., the level of encephalization), but simply correlateswith absolute brain size (Deaner et al., 2007) or with abso-lute numbers of cortical neurons and their connections andsynapses (Roth and Dicke, 2005). However, if advantages ofhigher encephalization or increased brain size are so obvi-ous, why big brains are so rare (Parker, 1990)? To answerthis paradox, one should obtain more detailed knowledge onneural scaling rules in various mammalian orders (Herculano-Houzel, 2011a,b), as well as ask what the costs of encephal-ization are and how they can be afforded (Foley and Lee,1991).

TOTAL NUMBER OF NEURONS IS MORE IMPORTANT THAN BRAIN SIZEper seIn a series of recent studies, starting with invention of newquantitative method for comparative analysis of cell and neu-ron numbers (Herculano-Houzel and Lent, 2005), it was clearlyrevealed that neural scaling rules evolved differently in different

mammalian orders, such as rodents and lagomorphs (Herculano-Houzel et al., 2006, 2011; Herculano-Houzel, 2007), insectivores(Sarko et al., 2009), and primates (Herculano-Houzel et al.,2007; Gabi et al., 2010) including great apes (Herculano-Houzeland Kaas, 2011) and humans (Azevedo et al., 2009; Herculano-Houzel, 2009). These studies pointed out that, in terms ofneuronal numbers, the human brain is linearly scaled-up pri-mate brain and that our superior cognitive abilities might simplyreflect the largest total number of neurons in the human brain(Herculano-Houzel, 2009, 2012a,b). It seems that basic primateadvantage consists in packing more neurons in the same brainvolume, thus avoiding prohibitively large increase in brain size(Herculano-Houzel, 2012a,b). In addition, human brains have∼3 times more brain neurons than gorillas and orangutans(Herculano-Houzel and Kaas, 2011). Another important find-ing concerns the coordinate increase in numbers of neurons inthe cerebral cortex and cerebellum and the fact that the vastmajority of all brain neurons are found in these two structures(Herculano-Houzel, 2009, 2010, 2011b, 2012a), thus supportingprevious findings on cerebral-cerebellar co-evolution (Whitingand Barton, 2003; Ramnani, 2006; Ramnani et al., 2006; Balsterset al., 2010). Therefore, it has been proposed that “the largerthe number of neurons in excess of that required to operate thebody, the more complex and flexible the behavior of an animalcan be expected to be, and thus the larger its cognitive abilities”(Herculano-Houzel, 2012a, p. 336).

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 1

HUMAN NEUROSCIENCE

Judaš et al. Subplate in human brain evolution

THE BRAIN IS EXPENSIVE TISSUE, AND ONLY MOTHERS AND INFANTSOF A “CHOSEN PRIMATE” CAN AFFORD TO GROW IT BEYONDORDINARY EXPECTATIONSHow much of the resting metabolic rate (RMR) is spend tomaintain the adult brain? While most mammals expend 3–4%of RMR on brain metabolism (Mink et al., 1981; Armstrong,1983, 1990), anthropoid primates spend about 8% of RMR tomaintain their brains (Armstrong, 1983, 1990; Hofman, 1983a,b;Martin, 1983; Leonard and Robertson, 1992; Genoud, 2002).While the large brain-body-mass ratio of humans (the adulthuman brain is 2% of the body’s mass) is not associated withelevations in RMR (Leonard and Robertson, 1992, 1994), adulthumans nevertheless expend two to three times more energy onbrain metabolism than other primates, that is 20–25% of RMR(Passmore and Durnin, 1955; Kety, 1957; Holliday, 1986; Aielloand Wheeler, 1995; Leonard et al., 1996; Rolfe and Brown, 1997;Genoud, 2002). These human brain costs are even more impres-sive during childhood, because the brain consumes roughly87% of RMR in the newborn, and 44% in a 5 year old child(Holliday, 1986). In comparison to the neonate chimpanzee, thecost of the human neonate brain is significantly greater, andby the age of 5 years these costs are 3 times as great (Foleyand Lee, 1991). Such energetic costs seem also to exert a selec-tive pressure toward metabolically efficient neural morphology,that is, metabolically efficient patterning of dendritic arboriza-tions (Wen and Chklovskii, 2008), neural codes (Levy and Baxter,1996; Balasubramanian et al., 2001), and brain wiring patterns(Chen et al., 2006).

Positive pleiotropic gene effects on relative brain and bodygrowth occur during prenatal and early postnatal periods,because genes affecting both traits generally do so during fetal andearly postnatal growth, when both brain and body size are grow-ing rapidly (Riska and Atchley, 1985).The fetal brain at any stageof development constitutes a markedly larger proportion of totalfetal weight in primates than in other mammals (Sacher, 1982),and this difference is still observable in neonates (Martin, 1983).However, this difference is no longer clear in comparisons amongadults, due to differential postnatal changes in different mammals(Martin, 1983). This points to the crucial importance of braindevelopment (Martin, 1996). For example, evolutionary shifts inbrain development lead to differences in development of socialbehavior and cognition even between such closely related speciessuch as chimpanzees and bonobos (Wobber et al., 2010).

The growth of the brain significantly depends upon energeticand hence ecological conditions (Martin, 1983; Foley and Lee,1991); as succintly stated by Foley and Lee (1991, p. 223): “what-ever selective pressures there may be driving the size of the brainup, these are satisfied only in the context of there being sufficientenergy.” Having a large brain imposes additional energetic costson both the infant and the mother; the mother can derive thatenergy either from the incorporation of higher quality food, fromfeeding for longer each day, or from maintaining lactation over alonger period (Foley and Lee, 1991). Thus, the evolution of a largebrain requires that energetic constraints are lifted (Armstrong,1983; Hofman, 1983a,b, 1993; Martin, 1983, 1996; Foley and Lee,1991; Leonard and Robertson, 1992, 1994; Aiello and Wheeler,1995; Leonard et al., 2003; Isler and van Schaik, 2006a,b, 2009).

Some recent evidence suggests that the metabolic cost may bean even more limiting factor to brain expansion than previouslysuspected (Herculano-Houzel, 2012b). Namely, the estimatedglucose use per neuron is remarkably constant, varying only by40% across the six species of rodents and primates, includinghumans (Herculano-Houzel, 2011c). Thus, it seems that the brainenergy budget per neuron is fixed across species and brain sizesand that the total metabolic cost of a brain is a simple, directfunction of its number of neurons (Herculano-Houzel, 2011c).These findings clearly suggest that neuronal metabolism imposesa series of constraints upon brain structure, function, and evo-lution (Herculano-Houzel, 2011c, 2012b; Fonseca-Azevedo andHerculano-Houzel, 2012). The metabolic constraints upon brainscaling in evolution are imposed by absolute number of neurons,because adding neurons to the brain comes at a sizable cost of 6kcal/d per billion neurons (Herculano-Houzel, 2011c).

Three major hypotheses have been proposed to explain howlarger brains are afforded among mammalian species (see Jonesand MacLarnon, 2004, for a comprehensive review): directmetabolic constraint hypothesis (Armstrong, 1983; Hofman,1983a,b); the expensive tissue hypothesis (Aiello and Wheeler,1995); and the maternal energy hypothesis (Martin, 1981, 1983,1996, 2007; Martin et al., 2005). None of these hypotheses hasthe general applicability in multiple mammalian clades with dif-ferent evolutionary histories (Jones and MacLarnon, 2004), andthere are several strategies for meeting the energetic demands ofencephalization which can be manifested differentially across taxa(Barrickman and Lin, 2010). However, at least in the case of large-brained apes and humans, the maternal energy hypothesis seemsto be well supported by the available evidence (Martin, 1996; Islerand van Schaik, 2006a,b, 2009; Isler et al., 2008). This hypoth-esis proposes that the brain size is constrained by the amountof energy that a mother can provide during the early stages ofher offspring’s ontogeny (Martin, 1996, 2007). It should be notedthat such a primary link between the mother’s metabolic capacityand the developing brain of her offspring allows other variablesto influence ultimate adult brain size (Martin, 1996). In addition,there may be no very tight relationship between relative brain sizeand specific behavioral capacities, and an increase in brain sizemay be advantageous in a diffuse fashion, i.e., may have somekind of permissive or promotive influence with respect to theevolution of cognition (Martin, 1996).

The encephalization is also associated with prolonged dura-tion of most life-history stages, especially in primates (Sacherand Staffeldt, 1974; Harvey and Clutton-Brock, 1985; Barton,1999; Kappeler and Pereira, 2003; Leigh, 2004; Barrickman et al.,2008) including humans (Bogin, 1997, 1999, 2009; Leigh, 2001).At least three changes in developmental timing occurred duringthe evolution of human encephalization: extended brain growth,retarded postnatal body growth, and a derived brain growthallometry (Vinicius, 2005). The human brain achieves its finalsize more by lengthening the time of growth than by adoptingan unusual rate of growth (Passingham, 1985). The prolongedperiod of growth in humans may be partly an adaptation tolimit the already high total and brain energy requirements duringchildhood (Leonard and Robertson, 1992). Others have suggestedthat selection has acted to decrease human somatic growth rates

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 2

Judaš et al. Subplate in human brain evolution

during childhood and juvenility (in comparison to chimpanzees),to help fuel the energy-expensive brain and to allow more time forincreased cognitive development with lower body-maintenancecosts (Walker et al., 2006).

So, how our evolving ancestors have solved the above men-tioned energetic challenges? Obviously, there were a number ofstep-wise changes, stretching perhaps over last 2 million years, i.e.,during the evolution of the genus Homo. One part of the solutionseems to be a significant change in dietary and foraging habits, ashumans have a much higher quality diet than expected for theirsize or their resting metabolic needs (Leonard and Robertson,1994, 1997; Fish and Lockwood, 2003). Turning to animal sourcefoods, such as meat, as a routine dietary component probablyrepresented an important step (Milton, 1999, 2003). However, itseems that a diet relying solely on consumption of raw food wasnot sufficient to remove this metabolic constraint on the increaseof brain size—as documented in a recent study, the largest greatapes cannot afford both a large body and a larger number ofbrain neurons (Fonseca-Azevedo and Herculano-Houzel, 2012).The use of fire and the invention of cooking might have asubstantial role, because the cooking increases enormously theenergy yield of foods and the speed with which they are con-sumed (Carmody and Wrangham, 2009; Carmody et al., 2011).While raw meat increased the caloric content of the diet of earlyhominids (Milton, 1999), the cooked meat is easier to chew andhas a higher caloric yield (Carmody et al., 2011). In fact, as themetabolic cost is limiting enough to impose tradeoffs in brainevolution (Fonseca-Azevedo and Herculano-Houzel, 2012), theinvention of cooking food was probably necessary to overcomesuch a metabolic limitation in the human lineage (Wranghamet al., 1999; Wobber et al., 2008; Carmody and Wrangham, 2009;Carmody et al., 2011). It should be also noted that there is evi-dence of up-regulation of genes related to energy metabolism inhuman evolution (Grossman et al., 2001; Cáceres et al., 2003;Uddin et al., 2004).

Another part of the solution seems to be represented by pro-found changes in the human life-history (Bogin, 1997, 1999,2001, 2009; Hawkes et al., 1998; Kaplan et al., 2000; Crews, 2003;Leigh, 2004; Gurven and Walker, 2006; Walker et al., 2006). Thereare several hypotheses on the evolution of human life-history,such as the grandmother hypothesis (Hawkes et al., 1998), theembodied capital hypothesis (Kaplan et al., 2000), the reservecapacity hypothesis (Crews, 2003; Larke and Crews, 2006), andthe reproductive fitness hypothesis (Bogin, 1997, 1999, 2009).Briefly, primates and other social mammals have three postna-tal life history stages: infancy, juvenile and adult (Pereira andFairbanks, 1993). However, human life history is characterizedby the addition of childhood, adolescence, and grandmotherhood(postmenopausal stage) as biologically, behaviorally, and math-ematically definable stages of the life cycle (Bogin, 1997, 1999;Hawkes et al., 1998). The transition from infancy (birth to 30–36months) to childhood is characterized by weaning and the com-pletion of deciduous tooth eruption (Bogin, 1999, 2001). Duringthe childhood, older members of the social group acquire, pre-pare, and provision foods to children, and this style of cooperativecare represents a major evolutionary invention in the human life-history (Bogin, 1999, 2009). The adolescence includes the years of

postpubertal growth (10–18 years for girls, 12–21 years for boys)(Bogin, 1999, 2001).

It is important to note that the childhood and adolescencestages of human life history evolved due to the selective advan-tages for increased fertility and reproductive fitness of mothers(Bogin, 1999, 2001, 2009), while the benefits of these stagesfor increased brain growth and learning are important, butsecondary, outcomes (Bogin, 2009). In summary, the humanspecies has more life stages than any other mammal and moretime for growth and development than any primate (Bogin,2009). Another important evolutionary novelty in human life-history is that human food provisioning and care to childrenand their mothers goes beyond the cooperative breeding of othermammals—humans use biological relationships and also mar-riage, systems of economic exchange, political power structure,and gender-role construction (Bogin, 2009). In other words,human life-history is culturally patterned (Bogin, 2001, 2009;Crews, 2003). Such investments of energy and care from prena-tal to early adult life stages build a greater level of reserve capacitythan found in any other primate (Crews, 2003; Larke and Crews,2006; Bogin, 2009).

THE SUBPLATE IS CRITICALLY INVOLVED IN THE ONTOGENESIS OF THEHUMAN CEREBRAL CORTEXThe data reviewed above clearly suggest that the developing brainplayed significant role in the evolution of the human life-history.As the telencephalon and the cerebral cortex represent by far thelargest part of the human brain, we here focus on the potentialevolutionary role of the transient subplate zone, because it is crit-ically involved in the development of the primate and humancerebral cortex (Bystron et al., 2008) and it reached a peak ofits evolutionary prominence in the human brain (Kostovic andRakic, 1990; Molnár et al., 2006; Rakic, 2006; Bystron et al., 2008).The role of the subplate in the development and plasticity ofthe cerebral cortex has been already well described in a numberof excellent reviews (Allendoerfer and Shatz, 1994; Kostovic andJudaš, 2002, 2006, 2007, 2010; Kanold and Shatz, 2006; Molnáret al., 2006; Rakic, 2006, 2009; Bystron et al., 2008; Kanold andLuhmann, 2010; Clowry et al., 2010; Judaš, 2011). Therefore, wewill here only briefly review those aspects of the human subplatewhich are directly relevant for understanding of our present the-sis. As the subplate development in the human brain has also beenextensively illustrated in our previous publications (Kostovic andRakic, 1980, 1990; Kostovic and Judaš, 2002, 2006, 2007, 2010;Judaš, 2011), we here provide only a few figures aimed to enhancethe understanding of our main argument.

The subplate zone was first described in the human fetal brain(Kostovic and Molliver, 1974; Judaš et al., 2010a; see, for a com-prehensive historical review). The subplate is the largest transientcompartment of the fetal neocortical anlage (see Judaš, 2011, fora comprehensive review). The human subplate develops between13 and 15 postconceptional weeks (PCW), remains the largestcompartment of the neocortical anlage between 15 and 30 PCW,and begins slowly to disappear toward the end of gestation andduring the early postnatal period (Figure 1). The developmen-tal peak of the subplate is reached during midgestation, when itis about four times thicker than the cortical plate (Figure 2). It

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 3

Judaš et al. Subplate in human brain evolution

FIGURE 1 | Laminar development of human telencephalon from 10

postconceptional weeks (PCW) to newborn. The layers are transient andtheir appearance changes with changes in neurogenetic events. Thesubplate starts to develop around 13 PCW, reaches the peak of itsdevelopment between 22 and 24 PCW, and starts to resolve around34 PCW. In the newborn brain, the subplate remains during the first year,when the subplate disappears as a zone but its neurons becomeincorporated into the subcortical white matter as so-called interstitialneurons. cp, cortical plate; sp, subplate zone; iz, intermediate zone; svz,subventricular zone; vz, ventricular zone. Bar = 100 µm (A), 250 µm (B),1 mm (C–E).

should be noted that the subplate is still present in the newbornbrain during the period when various corticocortical connectionscontinue to develop (Figure 3). Finally, many subplate neuronssurvive postnatally and eventually transform into interstitial neu-rons of the subcortical (gyral) white matter of the adolescentand adult brain (Figures 4, 5) (Kostovic and Rakic, 1980, 1990;Judaš et al., 2010b). While the dissolution of subplate begins dur-ing the last third of gestation, it remains present (as recognizablearchitectonic compartment) under the prefrontal and other asso-ciation cortices up to 6 postnatal months (Kostovic and Rakic,1990). It should be noted with a great regret that there are no dataavailable on the subplate of great apes; in fact, there are no his-tological data on any aspect of prenatal cortical development ingreat apes.

The subplate contains numerous neurons of various mor-phological types (Mrzljak et al., 1988, 1990, 1992) and molecu-lar phenotypes, including differentiated projection (glutamater-gic) neurons and local (GABA and peptidergic) interneurons(Judaš et al., 1999, 2010b; Judaš, 2011). It also serves as a wait-ing compartment for growing cortical afferents (Rakic, 1977;Kostovic and Rakic, 1990). Various afferent fibers sequentiallygrow into the subplate, establish temporary synaptic circuits,and “wait” in the subplate for several months before relocatinginto their final target, the cortical plate (Kostovic and Goldman-Rakic, 1983; Krmpotic-Nemanic et al., 1983; Kostovic and Rakic,1984, 1990; Kostovic, 1986). After 28 PCW, waiting associative

FIGURE 2 | Lamination of frontal (A), mid-central (B) and occipital (C)

region of human telencephalon at the peak of subplate development

(22–24 PCW), as revealed by Nissl staining and acetylcholinesterase

(AChE) histochemistry. At the peak of subplate development(22–24 PCW), subplate zone is the largest compartment of the humantelencephalon. It is the place of intense synaptic activity and “waiting”compartment for the thalamocortical fibers (dark band below cp). Note thatthere are regional differences in the lamination between frontal andoccipital region. cp, cortical plate; sp, subplate zone; iz, intermediate zone;svz, subventricular zone; vz, ventricular zone. Bar = 1 mm.

and commissural pathways are major constituents of the sub-plate (Kostovic and Rakic, 1990; Kostovic et al., 2008; Kostovicand Judaš, 2009). While long corticocortical pathways begin todevelop in the early fetal period (Vasung et al., 2010), the develop-ment of short corticocortical connections is very protracted andlasts for at least 1 year after birth (Kostovic et al., 2012). It shouldbe noted that cortical pyramidal neurons also require about 3years of postnatal development in order to attain their adult-likesize of dendritic arborization (Petanjek et al., 2008).

The subplate is also the major site of synaptogenesis in themidfetal brain (Molliver et al., 1973; Kostovic and Rakic, 1990)and contains diverse and transient neuronal circuits which rep-resent a neurobiological basis for transient electrophysiologicaland behavioral phenomena in fetuses and early preterm infants(Kostovic and Judaš, 2002, 2006, 2007, 2010). Although theonset of cortical synaptogenesis is an early fetal event (Molliveret al., 1973; Kostovic and Rakic, 1990), it should be noted thatcortical synaptogenesis is predominantly postnatal process andthat synaptic overproduction and developmental plasticity in thehuman cortex continue for at least 20 years (Petanjek et al., 2011).

The transformation of the fetal white matter occurs graduallyand in parallel with gradual dissolution of the subplate, and con-tinues postnatally (Judaš, 2011). The period spanning the last pre-natal month and at least the first postnatal year is characterized bysignificant fiber-architectonic reorganization at the cortical/whitematter interface (Kostovic et al., 2012). This reorganization is

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 4

Judaš et al. Subplate in human brain evolution

FIGURE 3 | Although the resolution of the subplate zone starts after 34

PCW, the subplate remains visible as a major component of the

telecephalic wall (asterisk in A,D). In the human telencephalon,cortico-cortical connections are still not developed (B) or myelinated (C) at33 PCW, while at 40 PCW substantial development and myelination ofcortico-cortical fiber can be observed (arrow in E,F). A–C 34 PCW, D–F

40 PCW.

FIGURE 4 | Subplate and white matter interstitial neurons stained for

NOS (NADPH-diaphorase-stained neurons in A–D), MAP2 (E,G) and

NeuN (F) are visible throughout the subplate (A,B) and the white

matter (C–G). Note that subplate/white matter interstitial neurons arenumerous even after the first year of life, when subplate zone disappears.(A), 37 PCW; (B), 13 days; (C), 12 years; (D), 57 years; (E,G), 13 months;(F), 51 years. Bar = 1 mm.

FIGURE 5 | Higher magnification view of subplate and white matter

interstitial neurons displayed in panels A–F of the Figure 4 and stained

for NOS (NADPH-diaphorase-stained neurons in A–D), MAP2 (E) and

NeuN (F). Note that dendritic arborizations of subplate/interstitial neuronscontinue to grow and develop even after the disapearance of the subplatezone during the first year of life (compare (A and B with C). (A), 37 PCW;(B), 13 days; (C), 12 years; (D), 57 years; (E), 13 months; (F), 51 years.Bar = 0.5 mm.

related to the postnatal persistence of the subplate remnant, theonset of myelination, the appearance of tertiary gyri and sulci,development of short corticocortical connections (Kostovic et al.,2012), and probably other factors, such as changes in microvas-cular network, changes in molecular profile of the extracellularmatrix, development of white matter astrocytes, and so forth(Judaš, 2011).

Thus, histogenetic processes in the human fetal and perinatalbrain are protracted and significantly overlap (Judaš, 2011), butthe subplate represents a playground for the majority of impor-tant events during that developmental window. The functionalsignificance of transient fetal circuitry and the pivotal role of thesubplate have already been extensively reviewed in both experi-mental model animals (Allendoerfer and Shatz, 1994; Kanold andLuhmann, 2010) and in humans (Kostovic and Judaš, 2006, 2007,2010; Judaš, 2011). Therefore, it will suffice to point out thatthe human perinatal and early postnatal period is characterizedby simultaneous existence of two separate (but interconnected)types of cortical circuitry organization: (a) transient fetal cir-cuitry, centered at the subplate zone, and (b) immature butprogressively developing permanent cortical circuitry, centered atthe cortical plate (that is, developing cortical layers I-VI). Thus,the developing human cortex passes through three major earlystages of functional development (Kostovic and Judaš, 2006, 2007,2010): (1) initial fetal circuitry which is endogeneously (spon-taneously) driven, (2) perinatal dual circuitry (co-existence ofendogeneously driven subplate-centered transient circuitry withdeveloping cortical plate-centered permanent circuitry) and (3)postnatally established permanent (externally driven) corticalcircuitry (Judaš, 2011).

THE SUBPLATE AS THE PLAYGROUND FOR EVOLUTION OF CORTICALDEVELOPMENTWhile the focus of this review is on putative (and relativelyrecent) evolutionary changes of the subplate in the primate and

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 5

Judaš et al. Subplate in human brain evolution

hominid lineage, it is important to note that the subplate mayhave a much older phylogenetic origin. As pointed out in severalrecent studies (Montiel et al., 2011; Wang et al., 2011), there arecurrently three hypotheses about the phylogenetic origin of sub-plate neurons: (1) subplate neurons were all already present inthe common ancestor of mammals and sauropsids (e.g., Marin-Padilla, 1978; Aboitiz et al., 2005); (2) subplate may be uniqueto mammals and represent an embryonic adaptation to sup-port development of increasingly complex neocortex (Kostovicand Rakic, 1990; Supér and Uylings, 2001; Molnár et al., 2006);and (3) the subplate in mammals may represent a combina-tion of new and ancestral cell populations (Aboitiz, 1999; Aboitizet al., 2005; Wang et al., 2011; Montiel et al., 2011). The thirdhypothesis suggests that, although embryonic subplate cells werepresent in the common ancestor of both mammals and saurop-sids, additional populations of subplate cells evolved in mammalsas the neocortex became progressively larger and more complex(Montiel et al., 2011; Wang et al., 2011). As the evolution ofthe mammalian cortex required the modification of developmen-tal programs, it seems probable that some of these started torely on novel populations of subplate neurons possibly charac-terized by different targets of connectivity (Kostovic and Rakic,1990; Montiel et al., 2011). Thus, it is important to determineif and how the subplate has been altered in distinct mammalianlineages and to perform comparative gene expression profilingstudies of subplate neurons in different species (Osheroff andHatten, 2009; Wang et al., 2010, 2011; Oeschger et al., 2012;Hoerder-Suabedissen et al., 2013). For example, species-specificdifferences in subplate markers have been described even betweenrat and mouse (Wang et al., 2011). In addition, in primates,in contrast to rodents, neurons are continuously added to thesubplate throughout cortical neurogenesis (Smart et al., 2002;Lukaszewicz et al., 2005; Molnár et al., 2006). Finally, in addi-tion to the increased number of neurons in the human subplate(Kostovic and Rakic, 1990; Smart et al., 2002; Bystron et al.,2008), there is both an increased complexity of subplate cell types(Kostovic and Rakic, 1990; Mrzljak et al., 1988, 1990, 1992; Wanget al., 2010) and subplate arrangements including the superfi-cial vs. deep compartmentalization of human subplate neurons(Wang et al., 2010).

Thus, the available evidence suggests that human subplatecontains an increased number of (ancestral and derived) sub-plate neurons as well as increased diversity of a derived pop-ulation of subplate neurons. As these neurons are active andtherefore metabolically expensive, the potential increase innumber of subplate neurons was probably subject to a sig-nificant selective pressure due to above described metabolicconstraints.

The lift-up of metabolic constraints by hominid ancestorsopened new vistas for the developing brain, because it becamepossible to metabolically support transient patterns of brain orga-nization as well as developmental brain plasticity for much longerperiod and with much greater number of neurons and connec-tivity combinations in comparison to apes. We propose that thetransient subplate zone and its postnatal remnant (interstitialneurons of the gyral white matter) probably served as the mainplayground for evolution of these developmental shifts, for thefollowing reasons.

First, as described above, the human brain contains aboutthree times more neurons than the brain of apes. As monkeyand human cortical neurons are all generated before birth (Rakic,2006, 2009; Bystron et al., 2008), and newborn human brain isalso significantly larger than that of newborn apes (ca. 350 vs. ca.200 g), it is logical to conclude that brains of human newbornsalso contain greatly increased number of neurons in compari-son to newborn apes. By extension, even if we assume that apeshave proportionately equally developed subplate, humans wouldstill have more numerous subplate neurons. Moreover, that hugenumber of subplate neurons is actively involved in shaping of cor-tical circuitry for at least 12 months (Judaš, 2011; Kostovic et al.,2012), and large number of subplate neurons survives into ado-lescence and adulthood as subcortical interstitial neurons (Judašet al., 2010b). Thus, significantly enlarged number of key playersin developmental cortical plasticity is present and metabolicallysupported to play this game for much longer than in any otherprimate species.

Second, as also described above, the subplate serves as a “wait-ing” compartment for numerous contingents of ingrowing cor-tical afferents. The human subplate contains the largest amountof both subcortical and corticocortical waiting afferents, dur-ing the longest developmental period. The subplate is the majorsite of synaptogenesis and early circuit formation during theprenatal period. Its circuitry also coexists with initial adult-likecircuitry during the perinatal period, and its neurons continue tobe involved in the development of short corticocortical connec-tions during the first postnatal year (Kostovic et al., 2012). Thus,humans become able to sustain an extremely long period of corti-cal circuitry development, characterized by large overproductionof axonal and dendritic branches, synapses and reorganizationalevents in response to environmental influences. This includesthe shaping of cortical connections through the interaction withinfant’s social environment, which probably enhanced typicallyhuman evolution of language, cognition and self-awareness.

In summary, we propose that life-history changes that enabledthe metabolic sustainability of prolonged retention of the subplatealso provided the playground for prolonged and more diverseperinatal and early postnatal plastic interactions between theincreased number of subcortical and corticocortical afferents andincreased number of cortical neurons (including the perinatal co-existence of fetal and adult-like cortical circuitry). This enabledthe evolution of new types of modular, areal and connectionalorganization of the human cerebral cortex, subserving cogni-tion and language. Our proposal is also in agreement with thereserve capacity hypothesis (Crews, 2003; Larke and Crews, 2006)and the reproductive fitness hypothesis (Bogin, 1997, 1999, 2001,2009), because the increased reserve capacity of human species(in comparison to apes) clearly enables the longer development ofthe human brain, with significant consequences for learning andsocialization as well as plasticity and recovery after brain lesions.

ACKNOWLEDGMENTSThis study has been supported by the Croatian ScienceFoundation (HZZ) Grant no. 09.01/414 to Miloš Judaš. Authorsgratefully acknowledge the technical assistance of DanicaBudinšcak and Zdenka Cmuk in the preparation of histologicalslides.

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 6

Judaš et al. Subplate in human brain evolution

REFERENCESAboitiz, F. (1999). Comparative

development of the mammalianisocortex and the reptilian dorsalventricular ridge. Evolutionaryconsiderations. Cereb. Cortex 9,783–791. doi: 10.1093/cercor/9.8.783

Aboitiz, F., Montiel, J., and Garcia, R.R. (2005). Ancestry of the mam-malian preplate and its deriva-tives: evolitonary relicts or embry-onic adaptations. Rev. Neurosci. 16,359–376.

Aiello, L. C., and Wheeler, P. (1995).The expensive tissue hypothesis:the brain and the digestive systemin human and primate evolution.Curr. Anthropol. 36, 199–221. doi:10.1086/204350

Allendoerfer, K. L., and Shatz, C.J. (1994). The subplate, a tran-sient neocortical structure: its rolein the development of connec-tions between thalamus and cortex.Annu. Rev. Neurosci. 17, 185–218.doi: 10.1146/annurev.ne.17.030194.001153

Armstrong, E. (1983). Relative brainsize and metabolism in mam-mals. Science 220, 1302–1304. doi:10.1126/science.6407108

Armstrong, E. (1990). Brains, bod-ies and metabolism. Brain Behav.Evol. 36, 166–176. doi: 10.1159/000115305

Azevedo, F. A. C., Carvalho, L. R. B.,Grinberg, L. T., Farfel, J. M., Ferretti,R. E. L., Leite, R. E. P., et al. (2009).Equal numbers of neuronal andnonneuronal cells make the humanbrain an isometrically scaled-up pri-mate brain. J. Comp. Neurol. 513,532–541. doi: 10.1002/cne.21974

Balasubramanian, V., Kimber, D.,and Berry, M. J. 3rd. (2001).Metabolically efficient informa-tion processing. Neural Comp.13, 799–815. doi: 10.1162/089976601300014358

Balsters, J. H., Cussans, E., Diedrichsen,J., Phillips, K. A., Preuss, T. M.,Rilling, J. K., et al. (2010). Evolutionof the cerebellar cortex: the selectiveexpansion of prefrontal-projectingcerebellar lobules. Neuroimage49, 2045–2052. doi: 10.1016/j.neuroimage.2009.10.045

Barrickman, N. L., Bastian, M. L., Isler,K., and van Schaik, C. P. (2008).Life history costs and benefits ofincreased brain size: a comparativetest using primates. J. Hum. Evol. 54,568–590. doi: 10.1016/j.jhevol.2007.08.012

Barrickman, N. L., and Lin, M. J.(2010). Encephalization, expensivetissues, and energetics: an exam-ination of the relative costs ofbrain size in Strepsirrhines. Am. J.

Phys. Anthropol. 143, 579–590. doi:10.1002/ajpa.21354

Barton, R. A. (1999). “The evolution-ary ecology of the primate brain,” inComparative Primate Socioecology,ed P. Lee (Cambridge: CambridgeUniversity Press), 167–194.

Bogin, B. (1997). Evolutionary hypo-theses for human childhood. Yearb.Phys. Anthropol. 40, 63–89.

Bogin, B. (1999). Evolutionary per-spective on human growth. Annu.Rev. Anthropol. 28, 109–153. doi:10.1146/annurev.anthro.28.1.109

Bogin, B. (2001). The Growth of Hum-anity. New York, NY: Wiley-Liss.

Bogin, B. (2009). Childhood, adoles-cence, and longevity: a multilevelmodel of the evolution of reservecapacity in human life history. Am.J. Hum. Biol. 21, 567–577. doi:10.1002/ajhb.20895

Bystron, I., Blakemore, C., and Rakic,P. (2008). Development of humancerebral cortex: Boulder Committeerevisited. Nat. Rev. Neurosci. 9,110–122. doi: 10.1038/nrn2252

Cáceres, M., Lachuer, J., Zapala, M.A., Redmond, J. C., Kudo, L.,Geschwind, D. H., et al. (2003).Elevated gene expression levels dis-tinguish human from non-humanprimate brains. Proc. Natl. Acad.Sci. U.S.A. 100, 13030–13035. doi:10.1073/pnas.2135499100

Carmody, R. N., Weintraub, G. S., andWrangham, R. W. (2011). Energeticconsequences of thermal and non-thermal food processing. Proc. Natl.Acad. Sci. U.S.A. 108, 19199–19203.doi: 10.1073/pnas.1112128108

Carmody, R. N., and Wrangham, R. W.(2009). The energetic significance ofcooking. J. Hum. Evol. 57, 379–391.doi: 10.1016/j.jhevol.2009.02.011

Chen, B. L., Hall, D. H., and Chklovskii,D. B. (2006). Wiring optimiza-tion can relate neuronal structureand function. Proc. Natl. Acad.Sci. U.S.A. 103, 4723–4728. doi:10.1073/pnas.0506806103

Clowry, G., Molnár, Z., and Rakic, P.(2010). Renewed focus on the devel-oping human neocortex. J. Anat.217, 276–288. doi: 10.1111/j.1469-7580.2010.01281.x

Crews, D. (2003). Human Senescence:Evolutionary and BioculturalPerspectives. Cambridge: CambridgeUniversity Press. doi: 10.1017/CBO9780511542350

Deaner, R. O., Isler, K., Burkart, J.,and van Schaik, C. (2007). Overallbrain size, and not encephalizationquotient, best predicts cognitiveability across non-human primates.Brain Behav. Evol. 70, 115–124. doi:10.1159/000102973

Fish, J. L., and Lockwood, C. A.(2003). Dietary constraints on

encephalization in primates. Am. J.Phys. Anthropol. 120, 171–181. doi:10.1002/ajpa.10136

Foley, R. A., and Lee, P. C. (1991).Ecology and energetics of encephal-ization in hominid evolution. Phil.Trans. R. Soc. Lond. B 334, 223–232.doi: 10.1098/rstb.1991.0111

Fonseca-Azevedo, K., and Herculano-Houzel, S. (2012). Metabolic con-straint imposes tradeoff betweenbody size and number of brain neu-rons in human evolution. Proc. Natl.Acad. Sci. U.S.A. 109, 18571–18576.doi: 10.1073/pnas.1206390109

Gabi, M., Collins, C. E., Wong, P.,Torres, L. B., Kaas, J. H., andHerculano-Houzel, S. (2010).Cellular scaling rules for the brainsof an extended number of primatespecies. Brain Behav. Evol. 76,32–44. doi: 10.1159/000319872

Genoud, M. (2002). Comparative stud-ies of basal rate of metabolismin primates. Evol. Anthropol. 11,108–111. doi: 10.1002/evan.10070

Grossman, L. I., Schmidt, T. R.,Wildman, D. E., and Goodman,M. (2001). Molecular evo-lution of aerobic energymetabolism in primates. Mol.Phylogenet. Evol. 18, 26–36. doi:10.1006/mpev.2000.0890

Gurven, M., and Walker, R. (2006).Energetic demand of multipledependents and the evolution ofslow human growth. Proc. R. Soc.B 273, 835–841. doi: 10.1098/rspb.2005.3380

Harvey, P. H., and Clutton-Brock, T. H.(1985). Life history variation in pri-mates. Evolution 39, 559–581. doi:10.2307/2408653

Hawkes, K., O’Connell, J. F.,Blurton Jones, N. G., Alvarez,H., and Charnov, E. L. (1998).Grandmothering, menopause, andthe evolution of human life histo-ries. Proc. Natl. Acad. Sci. U.S.A. 95,1336–1339.

Herculano-Houzel, S. (2007).Encephalization, neuronal excess,and neuronal index in rodents.Anat. Rec (Hoboken) 290,1280–1287. doi: 10.1002/ar.20598

Herculano-Houzel, S. (2009). Thehuman brain in numbers: a linearlyscaled-up primate brain. Front.Hum. Neurosci. 3:31. doi: 10.3389/neuro.09.031.2009

Herculano-Houzel, S. (2010).Coordinated scaling of corticaland cerebellar numbers of neu-rons. Front. Neuroanat. 4:12. doi:10.3389/fnana.2010.00012

Herculano-Houzel, S. (2011a). Notall brains are made the same:new views on brain scaling inevolution. Brain Behav. Evol. 78,22–36.

Herculano-Houzel, S. (2011b). Brainsmatter, bodies maybe not: the casefor examining neuron numbers irre-spective of body size. Ann. N.Y.Acad. Sci. 1225, 191–199.

Herculano-Houzel, S. (2011c). Scalingof brain metabolism with a fixedenergy budget per neuron: implica-tions for neuronal activity, plasticityand evolution. PLoS ONE 6:e17514.doi: 10.1371/journal.pone.0017514

Herculano-Houzel, S. (2012a).Neuronal scaling rules for pri-mate brains: the primate advantage.Prog. Brain Res. 195, 325–340.

Herculano-Houzel, S. (2012b). Theremarkable, yet not extraordinary,human brain as a scaled-up primatebrain and its associated cost. Proc.Natl. Acad. Sci. U.S.A. 109(Suppl. 1),10661–10668.

Herculano-Houzel, S., Collins, C. E.,Wong, P., and Kaas, J. H. (2007).Cellular scaling rules for primatebrains. Proc. Natl. Acad. Sci. U.S.A.104, 3562–3567. doi: 10.1073/pnas.0611396104

Herculano-Houzel, S., and Kaas, J. H.(2011). Gorilla and orangutanbrains conform to the pri-mate cellular scaling rules:implications for human evo-lution. Brain Behav. Evol. 77,33–44. doi: 10.1159/000322729

Herculano-Houzel, S., and Lent, R.(2005). Isotropic fractionator:a simple, rapid method for thequantification of total cell andneuron numbers in the brain.J. Neurosci. 25, 2518–2521. doi:10.1523/JNEUROSCI.4526-04.2005

Herculano-Houzel, S., Mota, B., andLent, R. (2006). Cellular scalingrules for rodent brains. Proc. Natl.Acad. Sci. U.S.A. 103, 12138–12143.doi: 10.1073/pnas.0604911103

Herculano-Houzel, S., Ribeiro, P. E. M.,Campos, L., da Silva, A. V., Torres, L.B., Catania, K. et al. (2011). Updatedneuronal scaling rules for the brainsof Glires (rodents/lagomorphs).Brain Behav. Evol. 78, 302–314. doi:10.1159/000330825

Hoerder-Suabedissen, A., Oeschger,F. M., Krishnan, M. L., Belgard,T. G., Wang, W. Z., Lee, S.,et al. (2013). Expression profil-ing of mouse subplate reveals adynamic gene network and dis-ease association with autism andschizophrenia. Proc. Natl. Acad.Sci. U.S.A. 110, 3555–3560. doi:10.1073/pnas.1218510110

Hofman, M. A. (1983a). Evolution ofbrain size in neonatal and adultplacental mammals: a theoreti-cal approach. J. Theor. Biol. 105,317–332.

Hofman, M. A. (1983b). Energymetabolism, brain size and

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 7

Judaš et al. Subplate in human brain evolution

longevity in mammals. Q. Rev.Biol. 58, 495–512.

Hofman, M. (1993). Encephalizationand the evolution of longevityin mammals. J. Evol. Biol. 6,209–277. doi: 10.1046/j.1420-9101.1993.6020209.x

Holliday, M. A. (1986). “Body com-position and energy needs dur-ing growth,” in Human Growth: AComprehensive Treatise, Vol. 2, 2ndEdn. eds F. Falkner and J. M. Tanner(New York, NY: Plenum), 101–117.

Isler, K., Kirk, E. C., Miller, J. M. A.,Albrecht, G. A., Gelvin, B. R., andMartin, R. D. (2008). Endocranialvolumes of primate species: scalinganalyses using a comprehensive andreliable dataset. J. Hum. Evol. 55,967–978. doi: 10.1016/j.jhevol.2008.08.004

Isler, K., and van Schaik, C. P. (2006a).Costs of encephalization: the energytrade-off hypothesis tested on birds.J. Hum. Evol. 51, 228–243.

Isler, K., and van Schaik, C. P. (2006b).Metabolic costs of brain size evolu-tion. Biol. Lett. 2, 557–560.

Isler, K., and van Schaik, C. P. (2009).The expensive brain: a frameworkfor explaining evolutionary changesin brain size. J. Hum. Evol. 57,392–400. doi: 10.1016/j.jhevol.2009.04.009

Jones, K. E., and MacLarnon, A. M.(2004). Affording larger brains: test-ing hypotheses of mammalian brainevolution on bats. Am. Nat. 164,E20–E31. doi: 10.1086/421334

Judaš, M. (2011). “Prenatal develop-ment of human fetal telencephalon,”in Fetal, MRI, Medical Radiology,ed D. Prayer (Berlin-Heidelberg:Springer Verlag), 81–146.

Judaš, M., Sedmak, G., and Pletikos,M. (2010a). Early history of sub-plate, and interstitial neurons: fromTheodor Meynert, (1867) to the dis-covery of the subplate zone (1974).J. Anat. 217, 344–367.

Judaš, M., Sedmak, G., Pletikos, M.,and Jovanov-Miloševic, N. (2010b).Populations of subplate and inter-stitial neurons in fetal and adulthuman telencephalon. J. Anat. 217,381–399.

Judaš, M., Šestan, N., and Kostovic, I.(1999). Nitrinergic neurons in thedeveloping and adult human telen-cephalon: transient and permanentpatterns of expression in compari-son to other mammals. Microsc. Res.Techn. 45, 401–419.

Kanold, P. O., and Luhmann, H. J.(2010). The subplate and early cor-tical circuits. Annu. Rev. Neurosci.33, 23–48. doi: 10.1146/annurev-neuro-060909-153244

Kanold, P. O., and Shatz, C. J.(2006). Subplate neurons regulate

maturation of cortical inhibitionand outcome of ocular dominanceplasticity. Neuron 51, 627–638. doi:10.1016/j.neuron.2006.07

Kaplan, H., Hill, K., Lancaster, J., andHurtado, A. M. (2000). A theory ofhuman life history evolution: diet,intelligence, and longevity. Evol.Anthropol. 9, 156–185.

Kappeler, P. M., and Pereira, M. E.(2003). Primate Life Histories andSocioecology. Chicago: University ofChicago Press.

Kety, S. S. (1957). “The generalmetabolism of the brain in vivo,” inMetabolism of the Central NervousSystem, ed D. Richter (New York,NY: Pergamon), 221–237.

Kostovic, I. (1986). Prenatal develop-ment of nucleus basalis complexand related fiber systems in man:a histochemical study. Neuroscience17, 1047–1077. doi: 10.1016/0306-4522(86)90077-1

Kostovic, I., and Goldman-Rakic, P.S. (1983). Transient cholinesterasestaining in the mediodorsalnucleus of the thalamus andits connections in the develop-ing human and monkey brain.J. Comp. Neurol. 219, 431–447. doi:10.1002/cne.902190405

Kostovic, I., Jovanov-Miloševic, N.,Radoš, M., Sedmak, G., Benjak,V., Kostovic-Srzentic, M., et al.(2012). Perinatal and early postna-tal reorganization of the subplateand related cellular compartmentsin the human cerebral wall asrevealed by histological and MRIapproaches. Brain Struct. Funct. doi:10.1007/s00429-012-0496-0490.[Epub ahead of print ].

Kostovic, I., and Judaš, M. (2002).Correlation between the sequentialingrowth of afferents and transientpatterns of cortical lamination inpreterm infants. Anat. Rec. 267, 1–6.doi: 10.1002/ar.10069

Kostovic, I., and Judaš, M. (2006).Prolonged coexistence of tran-sient and permanent circuitryelements in the developing cere-bral cortex of fetuses and preterminfants. Dev. Med. Child Neurol. 48,388–393. doi: 10.1017/S0012162206000831

Kostovic, I., and Judaš, M. (2007).Transient patterns of cortical lam-ination during prenatal life: dothey have implications for treat-ment. Neurosci. Biobehav. Rev.31, 1157–1168. doi: 10.1016/j.neubiorev.2007.04.018

Kostovic, I., and Judaš, M. (2009).“Early development of neuronalcircuitry of the human pre-frontal cortex,” in The CognitiveNeurosciences, 4th Edn, ed M. S.Gazzaniga (Cambridge, London:

A Bradford Book, The MIT Press),29–47.

Kostovic, I., and Judaš, M. (2010). Thedevelopment of the subplate andthalamocortical connections in thehuman foetal brain. Acta Paediatr.99, 1119–1127. doi: 10.1111/j.1651-2227.2010.01811.x

Kostovic, I., Judaš, M., and Petanjek,Z. (2008). “Structural developmentof the human prefrontal cortex,”in Handbook of DevelopmentalCognitive Neuroscience, 2nd Edn,eds C. A. Nelson and M. Luciana(Cambridge, London: A BradfordBook, The MIT Press), 213–235.

Kostovic, I., and Molliver, M. E. (1974).A new interpretation of the lam-inar development of cerebral cor-tex: synaptogenesis in different lay-ers of neopallium in the humanfetus. Anat. Rec. 178, 395.

Kostovic, I., and Rakic, P. (1980).Cytology and time of origin of inter-stitial neurons in the white matter ininfant and adult human and mon-key telencephalon. J. Neurocytol. 9,219–242. doi: 10.1007/BF01205159

Kostovic, I., and Rakic, P. (1984).Development of prestriate visualprojections in the monkey andhuman fetal cerebrum and adulthuman and monkey telencephalon.J. Neurosci. 4, 25–42.

Kostovic, I., and Rakic, P. (1990).Developmental history of the tran-sient subplate zone in the visualand somatosensory cortex of themacaque monkey and human brain.J. Comp. Neurol. 297, 441–470. doi:10.1002/cne.902970309

Krmpotic-Nemanic, J., Kostovic, I.,Kelovic, Z., Nemanic, D., andMrzljak, L. (1983). Developmentof the human fetal auditory cortex:growth of afferent fibres. Acta Anat.(Basel) 116, 69–73. doi: 10.1159/000145727

Larke, A., and Crews, D. E. (2006).Parental investment, late reproduc-tion, and increased reserve capac-ity are associated with longevity inhumans. J. Physiol. Anthropol. 25,119–131. doi: 10.2114/jpa2.25.119

Leigh, S. R. (2001). Evolution ofhuman growth. Evol. Anthropol. 10,223–236. doi: 10.1002/evan.20002

Leigh, S. R. (2004). Brain growth,life history and cognition in pri-mate and human evolution. Am. J.Primatol. 62, 139–164. doi: 10.1002/ajp.20012

Leonard, W. R., and Robertson, M.L. (1992). Nutritional require-ments and human evolution: abioenergetics model. Am. J. Hum.Biol. 4, 179–195. doi: 10.1002/ajhb.1310040204

Leonard, W. R., and Robertson, M.L. (1994). Evolutionary perspectives

on human nutrition: the influ-ence of brain and body size ondiet and metabolism. Am. J. Hum.Biol. 6, 77–88. doi: 10.1002/ajhb.1310060111

Leonard, W. R., and Robertson, M.L. (1997). Comparative primateenergetics and hominid evolu-tion. Am. J. Phys. Anthropol. 102,265–281.

Leonard, W. R., Robertson, M. L.,Aiello, L. C., and Wheeler, P. (1996).On diet, energy metabolism, andbrain size in human evolution.Curr. Anthropol. 37, 125–129. doi:10.1086/204476

Leonard, W. R., Robertson, M. L.,Snodgrass, J., and Kuzawa, C.(2003). Metabolic correlates ofhominid brain evolution. Comp.Biochem. Physiol. A 136, 5–15. doi:10.1016/S1095-6433(03)00132-6

Levy, W. B., and Baxter, R. A. (1996).Energy efficient neural codes.Neural Comp. 8, 531–535. doi:10.1162/neco.1996.8.3.531

Lukaszewicz, A., Savatier, P., Cortay, V.,Giroud, P., Huissoud, C., Berland,M., et al. (2005). G1 phase reg-ulation, area-specific cell cyclecontrol, and cytoarchitectonics inthe primate cortex. Neuron 47,353–364. doi: 10.1016/j.neuron.2005.06.032

Marin-Padilla, M. (1978). Dual ori-gin of the mammalian neocortexand evolution of the cortical plate.Anat. Embryol. 152, 109–126. doi:10.1007/BF00315920

Martin, R. D. (1981). Relative brain sizeand basal metabolic rate in terres-trial vertebrates. Nature 293, 57–60.doi: 10.1038/293057a0

Martin, R. D. (1983). Human BrainEvolution in an Ecological Context(52nd James Arthur Lecture on theEvolution of the Human Brain). NewYork, NY: American Museum ofNatural History.

Martin, R. D. (1996). Scaling of themammalina brain: the maternalenergy hypothesis. News Physiol. Sci.11, 149–156.

Martin, R. D. (2007). The evolutionof human reproduction: a prima-tological perspective. Yearb. Phys.Anthropol. 50, 59–84. doi: 10.1002/ajpa.20734

Martin, R. D., Genoud, M., andHemelrijk, C. K. (2005). Problemsof allometric scaling analysis:examples from mammalian repro-ductive biology. J. Exp. Biol. 208,1731–1747. doi: 10.1242/jeb.01566

Milton, K. (1988). “Foraging behaviourand the evolution of primateintelligence,” in MachiavellianIntelligence, eds R. W. Byrne and A.Whiten (Oxford: Clarendon Press),285–305.

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 8

Judaš et al. Subplate in human brain evolution

Milton, K. (1999). A hypothesis toexplain the role of meat-eating inhuman evolution. Evol. Anthropol.8, 11–21.

Milton, K. (2003). The critical roleplayed by animal source foods inhuman (Homo) evolution. J. Nutr.133, 3886S–3892S.

Mink, J. W., Blumenshine, R. J., andAdams, D. B. (1981). Ratio ofcentral nervous system to bodymetabolism in vertebrates: its con-stancy and functional basis. Am. J.Physiol. 241, R203–R212.

Molliver, M. E., Kostovic, I., and Vander Loos, H. (1973). The devel-opment of synapses in cerebralcortex of the human fetus. BrainRes. 50, 403–407. doi: 10.1016/0006-8993(73)90741-5

Molnár, Z., Métin, C., Stoykova, A.,Tarabykin, V., Price, D. J., Francis,F., et al. (2006). Comparative aspectsof cerebral cortical development.Eur. J. Neurosci. 23, 921–934. doi:10.1111/j.1460-9568.2006.04611.x

Montiel, J. F., Wang, W. Z., Oeschger,F. M., Hoerder-Suabedissen, A.,Tung, W. L., Garcia-Moreno, F.,et al. (2011). Hypothesis on thedual origin of the mammalian sub-plate. Front. Neuroanat. 5:25. doi:10.3389/fnana.2011.00025

Mrzljak, L., Uylings, H. B. M., Kostovic,I., and Van Eden, C. G. (1988).Prenatal development of neuronsin the human prefrontal cortex: I.a qualitative golgi study. J. Comp.Neurol. 271, 355–386. doi: 10.1002/cne.902710306

Mrzljak, L., Uylings, H. B. M., VanEden, C. G., and Judaš, M. (1990).Neuronal development in humanprefrontal cortex in prenatal andpostnatal stages. Prog. Brain Res. 85,185–222. doi: 10.1016/S0079-6123(08)62681-3

Mrzljak, L., Uylings, H. B. M., Kostovic,I., and Van Eden, C. G. (1992).Prenatal development of neurons inthe human prefrontal cortex. II. aquantitative golgi study. J. Comp.Neurol. 316, 485–496. doi: 10.1002/cne.903160408

Oeschger, F. M., Wang, W. Z., Lee,S., garcía-Moreno, F., Goffinet, A.M., Arbonés, M. L., et al. (2012).Gene expression analysis of theembryonic subplate. Cereb. Cortex22, 1343–1359. doi: 10.1093/cer-cor/bhr197

Osheroff, H., and Hatten, M. E.(2009). Gene expression profil-ing of preplate neurons destinedfor the subplate: genes involvedin transcription, axon extension,neurotransmitter regulation, steroidhormone signaling, and neuronalsurvival. Cereb. Cortex 19(Suppl. 1),i126–i134.

Parker, S. T. (1990) “Why big brainsare so rare?,” in Language andIntelligence in Monkeys andApes: Comparative DevelopmentalPerspectives, eds T. Parker and K.R Gibson (Cambridge: CambridgeUniversity Press), 129–154.

Passingham, R. E. (1985). Rates of braindevelopment in mammals includ-ing man. Brain Behav. Evol. 26,167–175. doi: 10.1159/000118773

Passmore, R., and Durnin, J. B. G.(1955). Human energy expenditure.Physiol. Rev. 35, 801–835.

Pereira, M. E., and Fairbanks, L. A.(eds.). (1993). Juvenile Primates: LifeHistory, Development, and Behavior.New York, NY: Oxford UniversityPress.

Petanjek, Z., Judaš, M., Kostovic, I., andUylings, H. B. M. (2008). Life-spanalterations of basal dendritic treesof pyramidal neurons in the humanprefrontal cortex: a layer-specificpattern. Cereb. Cortex 18, 915–929.doi: 10.1093/cercor/bhm124

Petanjek, Z., Judaš, M., Šimic, G.,Rašin, M. R., Uylings, H. B. M.,Rakic, P., and Kostovic, I. (2011).Extraordinary neoteny of synapticspines in the human prefrontal cor-tex. Proc. Natl. Acad. Sci. U.S.A.108, 13281–13286. doi: 10.1073/pnas.1105108108

Rakic, P. (1977). Prenatal developmentof the visual system in the rhesusmonkey. Philos. Trans. R. Soc. Lond.B 278, 245–260. doi: 10.1098/rstb.1977.0040

Rakic, P. (2006). A century of progressin corticoneurogenesis: from silverimpregnation to genetic engineer-ing. Cereb. Cortex 16, i3–i17.

Rakic, P. (2009). Evolution of the neo-cortex: a perspective from develop-mental biology. Nat. Rev. Neurosci.10, 724–735. doi: 10.1038/nrn2719

Ramnani, N. (2006). The primatecortico-cerebellar system: anatomyand function. Nat. Neurosci. 7,511–522. doi: 10.1038/nrn1953

Ramnani, N., Behrens, T. E., Johansen-Berg, H., Richter, M. C., Pinsk, M.A., Andersson, J. L., et al. (2006).The evolution of prefrontal inputsto the cortico-pontine system:diffusion imaging evidence frommacaque monkeys and humans.Cereb. Cortex 16, 811–818. doi:10.1093/cercor/bhj024

Riska, B., and Atchley, W. R. (1985).Genetics of growth predict patternsof brain-size evolution. Science 229,668–671. doi: 10.1126/science.229.4714.668

Rolfe, D. F. S., and Brown, G. C.(1997). Cellular energy utilizationand molecular origin of standardmetabolic rate in mammals. Physiol.Rev. 77, 731–758.

Roth, G., and Dicke, U. (2005).Evolution of the brain and intelli-gence. Trends Cogn. Sci. 9, 250–257.doi: 10.1016/j.tics.2005.03.005

Sacher, G. A. (1982). “The role ofbrain maturation in the evolutionof the primates,” in Primate BrainEvolution, eds E. Armstrong andD. Falk (New York, NY: Plenum),97–112.

Sacher, G., and Staffeldt, E. (1974).Relation of time to brain weightfor placental mammals: implica-tions for the theory of vertebrategrowth. Am. Nat. 108, 593–615. doi:10.1086/282938

Sarko, D. K., Catania, K. C., Leitch,D. B., Kaas, J. H., and Herculano-Houzel, S. (2009). Cellular scalingrules of insectivore brains. Front.Neuroanat. 3:8. doi: 10.3389/neuro.05.008.2009

Smart, I. H., Dehay, C., Giroud, P.,Berland, M., and Kennedy, H.(2002). Unique morphologicalfeatures of the proliferative zonesand postmitotic compartments ofthe neural epithelium giving rise tostriate and extrastriate cortex in themonkey. Cereb. Cortex 12, 37–53.doi: 10.1093/cercor/12.1.37

Supér, H., and Uylings, H. B. (2001).The early differentiation of the neo-cortex: a hypothesis on neocor-tical evolution. Cereb. Cortex 11,1101–1109. doi: 10.1093/cercor/11.12.1101

Uddin, M., Wildman, D. E., Liu, G.,Grossman, I. J., and Goodman, M.(2004). Sister grouping of chim-panzees and humans as revealedby genome-wide phylogenetic anal-ysis of brain gene expression pro-files. Proc. Natl. Acad. Sci. U.S.A.101, 2957–2962. doi: 10.1073/pnas.0308725100

Vasung, L., Jovanov-Miloševic, N.,Pletikos, M., Mori, S., Judaš, M.,and Kostovic, I. (2010). Prominentperiventricular fiber system relatedto ganglionic eminence and stria-tum in the human fetal cerebrum.Brain Struct. Funct. 215, 237–253.doi: 10.1007/s00429-010-0279-4

Vinicius, L. (2005). Human encephal-ization and developmental timing.J. Hum. Evol. 49, 762–776. doi:10.1016/j.jhevol.2005.08.001

Walker, R., Hill, K., Burger, O.,and Hurtado, A. M. (2006).Life in the slow lane revisited:ontogenetic separation betweenchimpanzees and humans. Am. J.Phys. Anthropol. 129, 577–583. doi:10.1002/ajpa.20306

Wang, W. Z., Hoerder-Suabedissen, A.,Oeschger, F. M., Bayatti, N., Ip,B. K., Lindsay, S., et al. (2010).Subplate in the developing cortexof mouse and human. J. Anat. 217,

368–380. doi: 10.1111/j.1469-7580.2010.01274.x

Wang, W. Z., Oeschger, F. M., Montiel,J. F., García-Moreno, F., Hoerder-Suabedissen, A., Krubitzer, L., et al.(2011). Comparative aspects of sub-plate zone studied with gene expres-sion in sauropsids and mammals.Cereb. Cortex 21, 2187–2203. doi:10.1093/cercor/bhq278

Wen, Q., and Chklovskii, D. B. (2008).A cost-benefit analysis of neuronalmorphology. J. Neurophysiol. 99,2320–2328. doi: 10.1152/jn.00280.2007

Whiting, B. A., and Barton, R. A.(2003). The evolution of thecortico-cerebellar complex in pri-mates: anatomical connectionspredict patterns of correlated evo-lution. J. Hum. Evol. 44, 3–10. doi:10.1016/S0047-2484(02)00162-8

Wobber, V., Hare, B., and Wrangham,R. (2008). Great apes prefer cookedfood. J. Hum. Evol. 55, 340–348. doi:10.1016/j.jhevol.2008.03.003

Wobber, V., Wrangham, R., and Hare,B. (2010). Bonobos exhibit delayeddevelopment of social behaviorand cognition relative to chim-panzees. Curr. Biol. 20, 226–230.doi: 10.1016/j.cub.2009.11.070

Wrangham, R. W., Jones, J. H., Laden,G., Pilbeam, D., and Conklin-Brittain, N. L. (1999). The raw andthe stolen. Cooking and the ecologyof human origins. Curr. Anthropol.40, 567–594. doi: 10.1086/300083

Conflict of Interest Statement: Theauthors declare that the researchwas conducted in the absence of anycommercial or financial relationshipsthat could be construed as a potentialconflict of interest.

Received: 25 March 2013; accepted: 14July 2013; published online: 02 August2013.Citation: Judaš M, Sedmak G andKostovic I (2013) The significance of thesubplate for evolution and developmen-tal plasticity of the human brain. Front.Hum. Neurosci. 7:423. doi: 10.3389/fnhum.2013.00423Copyright © 2013 Judaš, Sedmak andKostovic. This is an open-access arti-cle distributed under the terms of theCreative Commons Attribution License(CC BY). The use, distribution or repro-duction in other forums is permitted,provided the original author(s) or licen-sor are credited and that the originalpublication in this journal is cited, inaccordance with accepted academic prac-tice. No use, distribution or reproductionis permitted which does not comply withthese terms.

Frontiers in Human Neuroscience www.frontiersin.org August 2013 | Volume 7 | Article 423 | 9